Invention Development Program Helps Nurture NCI at Frederick Technologies

By John Hewes and Michele Newton, Contributing Writers; Karen Surabian, Guest Writer; and Brian O’Shea, Staff Writer
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The Invention Development Fund (IDF) was piloted by the Technology Transfer Center (TTC) in 2014 to facilitate the commercial development of NCI technologies. The IDF received a second round of funding from the NCI Office of the Director and the Office of Budget and Management to establish the Invention Development Program (IDP) for fiscal year 2016. The IDP is using these funds to help advance a second set of inventions.

Background

The co-development, or licensing, of NCI’s inventions with companies is often hindered by limited data that are directly relevant to commercial development. Recognizing this challenge, TTC sought funding and approval to implement the IDP. Managed by Technology Transfer Specialist John Hewes, Ph.D., the goal of the IDP is to accelerate the development of selected technologies through early stages of validation to inform critical decision points in the patenting process.  This is accomplished by providing funding needed to access studies conducted by Leidos Biomedical Research to demonstrate proof-of-principle for the invention.

Selecting Ideal Technologies for the Pilot Program

Beginning in 2014, TTC identified 21 inventions from NCI’s portfolio that were in need of specific data to attract commercial interest. TTC reviewed the selected inventions based on uniqueness, patent status, public health benefit, stage of research, patent filing date, and cost. Next, TTC established a Review Committee composed of NCI scientists with experience in drug development and preclinical validation to review the 21 inventions. Eight inventions emerged as top candidates for the program.

One of the benefits of the program is that inventors present their inventions to this Review Committee and receive verbal feedback about their invention and its developmental pathway from Review Committee discussions. IDP participants overwhelmingly agreed that the informal information exchange between the different disciplines that occurred during the interviews is a valuable asset of the program. These insights helped some inventors consider new opportunities for future development milestones that would help move an invention forward in the commercialization pipeline.

The eight technologies that moved forward in the pilot program are in various phases of in vivo studies. Four of the selected technologies are from Center for Cancer Research (CCR) scientists working in Frederick. As of this date, five inventions in the program have yielded actionable data.

“TTC recognizes the positive potential of IDP to further support the development of NCI inventions,” said TTC Associate Director Thomas Stackhouse. “We look forward to working with the NCI scientists and Leidos Biomedical staff to support these efforts.”

Inventor Viewpoints

Bruce Shapiro, Ph.D., senior investigator, Gene Regulation and Chromosome Biology Laboratory, CCR, NCI at Frederick, was chosen for his work on a mouse xenograft study.

Shapiro said he was pleased and excited upon hearing he had been selected for the IDP.

“[The IDP] provided the lab with an opportunity that would have been difficult to accomplish otherwise without the added support; for example, we were able to try our invention in various mouse experiments, which is giving us important new insights into future directions,” Shapiro said.

Anu Puri, Ph.D., staff scientist, Gene Regulation and Chromosome Biology Laboratory, CCR, NCI at Frederick, was also chosen by TTC for her project.

Puri said the funding provided by the IDP allowed her lab to analyze the drug distribution in various tissues, and the feedback from the Review Committee also proved beneficial.

“My presentation to the Review Committee brought up valid concerns and considerations to select suitable drug candidates for our dual drug delivery platform,” Puri said. “Information about the tumor models was very useful.”

The follow-up meetings with TTC staff, who helped plan and execute the experiments, and also monitored the progress of the project, were also beneficial aspects of the review, Puri said.

She added that she was “enthusiastically happy to receive this acknowledgment,” and that it “also provided motivation to continue to develop the technology that could be translated for patient care.”

David Wink Jr., Ph.D., deputy program director, Cancer and Inflammation Program, CCR, NCI at Frederick, was also chosen by TTC for his project.

Being selected for the IDP has dramatically accelerated critical animal models and the acquisition of much larger amounts of experimental compound to extend research into other cancer types, Wink said. He added that the feedback from the Review Committee was also valuable to the project.

“The most important aspect was [that] the committee distilled what was needed to advance the technology beyond simply publishing more papers,” Wink said. “They were a tremendous resource for how to advance here [at] NCI and who to contact.”

NCI Technologies in the Invention Development Pilot Program

Bruce Shapiro, “Targeted Nanoparticles for the Treatment of Virus-Infected or Cancerous Cells,” mouse xenograft study, CCR, NCI at Frederick

In the past several years, there has been a significantly increased interest in using RNA interference (RNAi) for biomedical applications, Shapiro said. RNAi is a post-transcriptional sequence with a specific process of gene silencing that employs double-stranded RNAs (dsRNAs) and a set of specific proteins and enzymes. 

Shapiro’s invention involves splitting the functionality of Dicer substrate siRNAs (or traditional siRNAs) into two R/DNA hybrids. When there is a simultaneous presence inside the same diseased cell, they will recognize each other through a toehold interaction within the DNA portion, and re-associate into RNA and DNA duplexes due to the thermodynamic differences between RNA and DNA, thus releasing the Dicer substrate siRNA.

“Besides allowing for additional control over the RNAi activation, this new approach may also help to overcome some challenges currently associated with the stability and delivery of siRNAs [such as intravascular degradation],” Shapiro said. “This technology is applicable to target multiple genes of interest simultaneously.”

Shapiro and his team have performed initial mouse studies using the HT29 tumor xenografts to validate their technology, he said. Based on the initial screening, further experiments have been planned and scheduled. The Review Committee suggested they focus on this invention as part of the IDP, as opposed to others in their portfolio, which allowed them to pursue new avenues that were previously unexplored.

Anu Puri, “Photoactivatable Nanoparticles for Targeted Drug Delivery,” analysis of tumor tissue (fluorescence), CCR, NCI at Frederick

The field of cancer nanomedicine is considered a promising area for improved delivery of bioactive molecules, including drugs, pharmaceutical agents, and nucleic acids, Puri said. Nanoparticulate systems comprising unique lipid assemblies (primarily liposomes) are currently in use for patient care. However, developing viable methods for on-demand spatial and temporal release of entrapped drugs is likely to have a significant impact on the clinical suitability of the nanomedicine, she said.

“One such approach utilizes light as the external stimulus, to selectively disrupt and/or destabilize drug-loaded nanoparticles in the tumor area,” Puri said. However, she noted that the success of light-guided therapy depends on the choice of adequate light sources that can penetrate the tissues (? 1 cm depth). This invention is an effort towards the development of novel lipid-based nanoparticles for on-demand drug delivery.

David Wink Jr., “Novel Nitroxyl (HNO) Prodrugs and Biomedical Applications Thereof,” production of compound and mouse xenograft study, CCR, NCI at Frederick

Wink said cyclooxygenase inhibitors have been shown to reduce cancer incidence as well as improve the outcome of conventional therapy. Some of the drawbacks to chronic high doses of common nonsteroidal anti-inflammatory drugs (NSAIDs) include toxicity related to the gastrointestinal tract and an increased risk of thrombosis, which can lead to an increased risk of stroke and heart attack.

Improvements to NSAIDs, such as aspirin or ibuprofen, that prevent gastrointestinal toxicity and thrombosis, have been a critical area of development. NSAIDs that are modified with moieties that release small molecules like nitric oxide (NO) have been effective in abating these toxicities. Wink said the invention showed that NSAIDs that release HNO, a one-electron reduction product of NO, were equally safe.  In addition, these compounds specifically killed cancer cells, but were nontoxic to the animal. This invention has found a novel approach to targeting cancer cells in a safer manner than over-the-counter NSAIDs, he said.

Additional Technologies Selected for the Invention Development Program

John Beutler, Ph. D., associate scientist, Molecular Targets Laboratory, CCR, NCI at Frederick, “Englerin A Efficacy beyond 786-0 Kidney and PC-3 Prostate Cancers,” mouse xenograft study

Ludmila Prokunina-Olsson, Ph.D., senior investigator, Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, NCI, “Genetic Marker for Predicting Viral Clearance in Patients Infected with Hepatitis C Virus (HCV),  Discovery of Novel interferon, IFN-?4, Development of Monoclonal Antibodies and Recombinant Biologically Active Protein,” RNA sequencing and production of protein biomarker

Jay Berzofsky, M.D., Ph.D., chief, Vaccine Branch, CCR, NCI, “Modified POTE Peptide Vaccine against Cancer of the Prostate, Colon, Lung, Breast, Ovary, and Pancreas,” peptide modification/production

Len Neckers, Ph.D., senior investigator, Urologic Oncology Branch, CCR, NCI, “Compounds That Interfere with the Androgen Receptor Complex: Use in Treating Prostate Cancer or Enlargements, Diabetes, and as Contraceptives,” mouse xenograft study

Mitchell Ho, Ph.D., investigator, Laboratory of Molecular Biology, CCR, NCI, “High-Affinity Human Monoclonal Antibodies to Glypican-3 for Liver Cancer Therapy and Diagnosis,” monoclonal antibody production for mouse xenograft studies

Karen Surabian is a licensing and patenting manager at the NIH Office of Technology Transfer.

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